Mercury intoxication in rodents causes damage to various organs including the brain via oxidative stress. Aqueous extract of
Telfairia occidentalis
(TOAE) may be a preventive agent by virtue of its reported antioxidant property. The present study was carried out to investigate the possible protective role of TOAE against mercuric chloride (HgCl
2)-induced changes in rat brain. Twenty-four adult female rats (150g-200g) were randomized into four groups of six rats each after acclimatization viz: I: Control, tap water; II: TOAE (400 mg/kg body wt.); III: HgCl
2 (4 mg/kg body wt.); IV: TOAE (400 mg/kg body wt.) + HgCl
2 (4 mg/kg body wt.). All treatments were oral by gastric gavage and lasted 14 days. Behavioural tests were conducted on the 15
th day after which rats were euthanized with i.p Ketamine (100mg/kg) same day. Brain weight, antioxidant parameters [malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and super oxide dismutase (SOD)], behavioural studies, and histology of rat hippocampus and cerebellum with regard to micro-anatomical parameters were examined in all groups. Mercuric chloride (HgCl
2) induced significant (p<0.0.05) elevation of the MDA level, activities of CAT and SOD, grooming and locomotion frequency but reduced GSH level relative to control. Also, it induced the death of granule cells, pyramidal cells and Purkinje neurons thus altering the microanatomy of these brain structures. However, concomitant administration of TOAE with HgCl
2 caused a reversal of these parameters relative to HgCl
2.–treated rats. In conclusion, aqueous extract of
Telfairia occidentalis demonstrated protective effects against HgCl
2-induced oxidative and histological changes of the microanatomy of rat hippocampus and cerebellum.